Antioxidant Enzyme Activity and Cognition in Obese Individuals with or without Metabolic Risk Factors.

Background: The metabolic syndrome may be associated with cognitive impairment and increased oxidative stress. Aim: To document the association between metabolic syndrome, cognitive impairment and oxidative stress activity in metabolically healthy obese and in metabolically unhealthy obese individuals. Methods: 60 obese individuals aged (49±10 years, 52% male) were enrolled. Obesity was defined as BMI>30. Metabolic syndrome was defined according to ATP III guidelines. Obese individuals were divided into 2 groups: Group 1, metabolically healthy obese (≤2 components of metabolic syndrome), and Group 2, metabolically unhealthy obese (>2 components of metabolic syndrome). Cognitive dysfunction was determined by Montreal cognitive assessment score. Liver Fibro scan (Elastography), Inflammation (CRP), pro oxidants (MDA), antioxidant activity (SOD, PON, GSH, GPx) and insulin resistance (HOMA-IR) were measured. Results: Of the 30 metabolically unhealthy obese individuals, 13% developed dementia, 51% had mild cognitive impairment, and 36% had a normal cognitive score. In the metabolically healthy obese group, 3% developed dementia, 7% had mild cognitive impairment, and 90% had a normal cognitive score. There was a significant difference in liver stiffness (7±3 vs. 5.2±2.7 kpa, p<0.001), liver fat measurement (337±51 vs. 280±20 db/m, p<0.001), MDA (4.7±0.9 vs. 5.47±1.12 mM, P<0.003), Glutathione GSH (27.2±2.4 vs. 28.4±2.3, P<0.03), CRP (9±6 vs. 7±6 P<0.001) and insulin resistance (2.5±1 vs. 6±5.5 p<0.02) between the 2 groups. Correlations were significant between GPx activity and liver stiffness (r=0.37), GPx activity and abdominal girth (r=-0.22) and glucose concentration and SOD activity (r=0.4). Multivariate analysis showed that HOMA-IR, MDA and GSH were the most powerful predictors of metabolically unhealthy obesity. Conclusion: There is a significant mild cognitive impairment and increased oxidative stress activity in the metabolically unhealthy obese. Whether treatment with anti-oxidants improves cognitive dysfunction remains to be determined.

Correlation between changes in liver stiffness and preeclampsia as shown by transient elastography.

OBJECTIVE: The aim of this study was to evaluate the use of Fibroscan as a measure of liver transient elastography in women with preeclampsia and compare the results with a group of normotensive controls. MATERIALS AND METHODS: In this prospective observational case-control study, women at 24-41 weeks gestation who were diagnosed with preeclampsia using standard criteria, between January 2012 and December 2013, were included. The Fibroscan test was performed by a hepatologist 1-7 days postpartum. A control group consisted of low-risk women with normal pregnancy outcomes. RESULTS: Fibroscan results for fibrosis were significantly higher in the 32 preeclamptic women compared to the 16 normotensive women (mean 4.57 kPa vs. 3.66 kPa respectively, P = 0.01). There was no difference in liver steatosis between women with preeclampsia and normotensive women (226 vs. 225 kPa, respectively, P = 0.442) Conclusions: Fibroscan results for fibrosis were significantly higher in postpartum preeclamptic women (although within the normal range). Further studies are required in order to evaluate the usefulness of Fibroscan as an additional test in the evaluation and management of preeclampsia.

Epicardial fat, rather than pericardial fat, is independently associated with diastolic filling in subjects without apparent heart disease.

BACKGROUND AND AIM: Epicardial and pericardial fat are separate fat depots surrounding the heart. Previous studies found epicardial fat to be associated with diastolic dysfunction, but they had some limitations. Pericardial fat association with diastolic dysfunction was not examined. Our aim was to assess the relation of epicardial and pericardial fat with diastolic filling. METHODS AND RESULTS: In 73 volunteers without known heart disease or complaints, using echocardiography, we measured epicardial and pericardial fat thickness from long(LAX) and short(SAX) axis views and assessed diastolic filling: mitral inflow (E/A ratio, E wave deceleration time[DT]), pulmonary vein flow (systolic/diastolic ratio [S/D], systolic filling fraction[SFR], late retrograde velocity[Ar]), color M-mode flow propagation velocity [Vp], and tissue Doppler derived mitral early annular velocities at the septum [e' sep] and lateral wall [e'-lat]. By Spearman's correlation, epicardial fat from LAX had a weak, but statistically significant correlations with several diastolic filling indices (SFR{rs = 0.29, P = 0.02}, Ar{rs = 0.3, P = 0.01}, Vp{rs = -0.3, P = 0.01}, e' sep{rs = -0.23, P = 0.04}, e' lat{rs = -0.26, P = 0.03}). In multivariate logistic regression model adjusting for age, gender, diabetes, systolic blood pressure and left ventricle mass index, epicardial fat thickness from LAX (and not from SAX) was the only independent predictor of e' [e' sep < 8: OR = 1.8, 95%CI = 1.1-2.9; e' lat<10: OR = 1.6, 95%CI = 1.01-2.6]. After adjustment, Pericardial fat measured from LAX was independent predictor of e' lat only[e' lat < 10:OR = 1.3, 95% CI 1.03-1.6). CONCLUSIONS: Epicardial fat measured from LAX is an independent predictor of myocardial relaxation. Pericardial fat independent association with diastolic filling is uncertain.

On the association between soft drink consumption and Helicobacter pylori infection.

BACKGROUND: The association between soft drink (SD) consumption and Helicobacter pylori infection remains unclear. AIM: To examine the relationship between SD consumption and H. pylori infection. METHODS: A prospective study included individuals who were referred for an upper gastrointestinal endoscopic examination because chronic dyspepsia within a period of 1 year. In addition to determining daily SD consumption and the risk factors for H. pylori infection by asking all study participants to complete a standard questionnaire about their diet, daily eating and drinking habits, and their lifestyle before undergoing the endoscopic examination. H. pylori infection was established by a positive result of the rapid urease test and histology. RESULTS: Of the 312 individuals who were referred for the endoscopic examination because chronic dyspepsia, 269 met the inclusion criteria. H. pylori infection was found in 164 (61%) of the 269 study participants, and, of these, 104/164 individuals were SD consumers with H. pylori infection versus 24/105 individuals without H. pylori infection (63 vs. 23%, respectively, P < 0.001). The results of the multiple logistic regression analysis showed that SD consumption (odds ratio = 4.0; 95 % confidence interval = 3.19­5.82,P < 0.001), was associated with H. pylori infection. CONCLUSION: SD consumption is associated with H. pylori infection in individuals with chronic dyspepsia.

The impact of prior long-term versus short-term statin use on the mortality of bacteraemic patients.

BACKGROUND: The aim of this investigation was to assess the effect of prior statin use on the 30-day in-hospital mortality among bacteraemic patients and to determine the impact of long-term versus short-term statin use on the mortality of bacteraemic patients. PATIENTS AND METHODS: A retrospective study of 342 bacteraemic patients who presented to the emergency department (ED) within a period of 7 years was undertaken. Twenty-three patients did not meet the inclusion criteria. The remaining 319 patients were divided into three groups according to statin use and duration of therapy prior to the bacteraemic episode: group 1 (n = 123) had long-term statin use ≥ 12 weeks, group 2 (n = 35) had short-term statin use < 12 weeks, and group 3 (n = 161) had no statin use. RESULTS: The overall 30-day in-hospital all-cause mortality of patients with statins was lower than patients without statin therapy (13 vs. 24%, p = 0.001). The mortality rate in group 1 was lower than in group 2 (11 vs. 17%, p = 0.04). After adjusting for confounding variables, the results of a multiple Cox regression analysis revealed that the absence of statin use (hazard ratio [HR] = 2.98; 95% confidence interval [CI] 1.59-5.56, p = 0.001) was associated with increased 30-day in-hospital all-cause mortality in bacteraemic patients. CONCLUSIONS: Statins reduce the 30-day in-hospital all-cause mortality of bacteraemic patients. Long-term statin use prior to the bacteraemia improves the survival of bacteraemic patients more than short-term statin use.

Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease.

The most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is coronary artery disease (CAD), not chronic liver disease. Fatty liver increases cardiovascular risk by classical (dyslipidemia, hypertension, diabetes) and by less conventional mechanisms. Common pathways involved in the pathogenesis of fatty liver and CAD includes hepatic insulin resistance and sub clinical inflammation. The hepatic insulin resistance state of fatty liver infiltration is characterized by increased FFA, which causes lipotoxicity and impairs endothelium-dependent vasodilatation, increases oxidative stress, and has a cardio toxic effect. Additional metabolic risk factors include leptin, adiponectin, pro inflammatory cytokines [such as IL-6, C-reactive protein and plasminogen activator inhibitor-1 (PAI-1)], which together lead to increased oxidative stress and endothelial dysfunction, finally promoting coronary artery disease (CAD). When classical risk factors are superimposed on fatty liver accumulation, they may further increase the new metabolic risk factors, exacerbating CAD. The clinical implication is that patients with NAFLD are at higher risk (steatohepatitis, diabetes, obesity, atherogenic dyslipidemia) and should undergo periodic cardiovascular risk assessment including the Framingham score, cardiac effort test, and measurement of intimae-media thickening of the carotids arteries. This may improve risk stratification for CAD.

Reactivation versus primary CMV infection after splenectomy in immunocompetent patients.

Acute CMV infection in the immunocompetent host is usually asymptomatic or produces only mild symptoms. CMV infection in immunocompromized patients, especially transplant recipients and those infected with HIV, is a result of profound lymphopenia or dysfunction of CD4+/CD8+ cells and can cause substantial rates of complication and death. We present a case of CMV infection in a previously healthy man who just had splenectomy for blunt trauma: a short incubation of the CMV disease, a strongly positive CMV antigenemia, severity of the disease including prominent lymphocytosis, massive hepatic sinusoidal infiltration, and retinitis. Splenectomy changed the immunological defense against the virus and brought the infection to nearly fulminant scale.

Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases.

AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Forty-four patients with chronic hepatitis (28 men and 16 women, with mean age of 45+/-11 and 49+/-12 years, respectively) constituted the patient population of this study. The groups were divided as follows: 15 patients with fatty liver (FL); 15 with non-alcoholic steatohepatitis (NASH); 14 with chronic viral hepatitis (CH) diagnosed by histology and liver technetium scan or ultrasound; and 10 healthy individuals. Thrombophilic, coagulation factors and genetic mutations were diagnosed by standard hemostatic and molecular coagulation assays. RESULTS: Activated protein C (APC) resistance and protein S were the most prevalent thrombotic risk factors (6% and 10% in NAFLD vs 21% and 14% in CH; P<0.01 and P<0.05, respectively). One thrombotic risk factor was identified in 41% of patients (23% mild fibrosis, 18% severe fibrosis) and two thrombotic risk factors in 6% of patients with NAFLD and severe fibrosis. While no differences in APC ratio, lupus anticoagulant, fibrinogen, factor V Leiden, prothrombin, and MTHFR mutation were found. Protein S levels were significantly lower in NASH patients than in patients with FL alone (92+/-19 vs 106+/-2, P<0.01). Protein C levels were markedly higher in patients with NAFLD and mild or severe fibrosis as compared to the patients with CH, respectively (128+/-40 vs 96+/-14, P<0.001 or 129+/-36 vs 88+/-13, P<0.01). CONCLUSION: Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis, suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.

Viral hepatitis and the surgeon.

BACKGROUND: Viral hepatitis is an infection of the liver caused by one or more of six known (HAV-HGV) hepatotropic viruses. It is a common problem among health care workers and their patients. Surgeons are at particular risk of both acquiring and transmitting some of these viruses from and to their patients. Unfortunately, specific immunoprophylaxis for viral hepatitis is presently limited to protecting against the spread of hepatitis A and B viral infections, leaving a high degree of vigilance and careful surgical technique as the only means available to prevent the transmission of other viruses relative to the surgeon. The purpose of this paper is to review the various forms of viral hepatitis including the nature of the virus, serologic testing, clinical features, epidemiology (with specific reference to those issues that arise in surgical practice), treatment and prevention.

Vascular endothelial growth factor and angiopoietin in liver regeneration.

Liver architecture remodeling following partial hepatectomy (PHx) involves the formation of a complex network of liver sinusoids through which the blood flows. The present study examines the involvement of vascular endothelial growth factor (VEGF) and angiopoietin-1 (ang-1) during liver regeneration. Following PHx, VEGF and ang-1 mRNA levels increase, followed by gradual return to baseline levels. RT-PCR analysis of VEGF mRNA reveals three isoforms, VEGF120, VEGF164 and VEGF188. Of the three, VEGF188 is the predominant isoform, VEGF120 being the less abundant. Although VEGF mRNA fluctuates following PHx, the relative expression of each isoform remains the same throughout the recovery process. The level of neuropilin-1, an accessory receptor of VEGF to main receptor corresponds with that of VEGF and ang-1. We have previously demonstrated the capacity of exogenous VEGF165 to stimulate liver cell proliferation following PHx. We now report similar effect using VEGF121, further demonstrating the benefit of manipulating growth factors where such an intervention is required.

Fatty infiltration of liver in hyperlipidemic patients.

Hyperlipidemia is a known risk factor for fatty infiltration of the liver, a condition that can progress to cirrhosis and liver failure. The objectives of this study were to document the prevalence of fatty infiltration in the livers of hyperlipidemic patients and to identify the predictor variables associated with this condition. Over an 18-month recruitment period, clinical, biochemical, and radiologic assessments were performed in a cross-sectional manner in 95 adult patients referred to an urban hospital-based lipid clinic for evaluation and management of hyperlipidemia. The mean (+/-SD) age of the patients was 55 +/- 13 years. Forty-eight (51%) were male. Fifty-two patients (55%) had hypercholesterolemia, 25 (26%) severe hypertriglyceridemia, 14 (15%) mixed hyperlipidemia, and 4 (4%) moderate hypertriglyceridemia. Obesity and diabetes were present in 36 (38%) and 12 (12%) of cases, respectively. A total of 61 (64%) patients had elevated liver enzyme tests. The most common enzyme abnormalities were an elevated serum ALT in 45 (47%) and GGT in 43 (45%) of patients. Ultrasound findings revealed diffuse fatty liver in 47 patients (50%), of which 21 cases (22%) were mild, 18 (19%) moderate, and 8 (9%) severe. The majority of patients with hypercholesterolemia [35/52 (67%)] had normal ultrasounds, whereas severe hypertriglyceridemia and mixed hyperlipidemia were frequently associated with radiologic evidence of fatty liver (odds ratios 5.9 and 5.1 respectively, P < 0.01). Independent predictors of fatty liver were; AST (P = 0.001), hyperglycemia (P = 0.02), and age (P = 0.04). In a model incorporating known risk factors for fatty liver, diabetes was the only risk factor other than hypertriglyceridemia that was significantly associated with fatty infiltration. No such effect was seen with age, gender, obesity, or alcohol consumption. In conclusions, the results of this study indicate that ultrasonographic evidence of fatty infiltration of the liver is evident in approximately 50% of patients with hyperlipidemia. Hypertriglyceridemia is the lipid profile most often associated with this condition. Serum AST values, hyperglycemia, and age independently predict the presence of fatty infiltration, while hypertriglyceridemia and diabetes are the only risk factors that significantly increase the risk of fatty infiltration in hyperlipidemic patients.

Serum aspartate but not alanine aminotransferase levels help to predict the histological features of chronic hepatitis C viral infections in adults.

OBJECTIVES: The aims of this study were to assess the predictive values of age, gender, route of transmission, extent of steatosis, alcohol consumption, and serum aminotransferase values on the histological findings in patients with chronic hepatitis C viral infections. METHODS: We retrospectively reviewed the charts and liver biopsy findings from 79 adult patients with serological evidence of chronic hepatitis C viral infections. RESULTS: The mean (+/- SD) age of the patient population was 43.5 +/- 10.8 yr; 47 patients (60%) were male. The routes of transmission were considered to be parenteral drugs in 44 patients (56%), previous blood transfusions in 25 (32%), and miscellaneous parenteral and nonparenteral routes in 10 (13%). The mean histological activity score of the group as described by Desmet et al. was 3.5 +/- 0.8 (maximum possible score, 18) and the fibrosis score 1.5 +/-0.4 (maximum possible score, 4), indicating relatively mild disease in the majority of cases. The extent of inflammation correlated with fibrosis (r = 0.72). By multivariate stepwise regression analyses, serum aspartate aminotransferase (AST) values emerged as the most important predictive variable of histological activity (r = 0.62). When overall histological activity was further divided into portal inflammation, piecemeal necrosis, and lobular activity, correlations were found between AST values and portal inflammation (r = 0.58) and piecemeal necrosis (r = 0.61) but not lobular activity (r = 0.1). A correlation was also observed between AST values and the extent of hepatic fibrosis (r = 0.64). On the other hand, serum ALT values did not correlate with histological activity but did correlate weakly with the extent of hepatic fibrosis (r = 0.39 and 0.51, respectively). There were no significant correlations between age, gender, route of transmission, steatosis, or alcohol consumption with the extent of histological activity or fibrosis. CONCLUSIONS: Serum AST values correlate well with two of three features of hepatic inflammation and with the extent of hepatic fibrosis. These findings suggest that, among other factors, serum AST values should be considered in decisions regarding the need for liver biopsy and treatment in patients with chronic hepatitis C viral infections.

Increased GABAergic activity inhibits alpha-fetoprotein mRNA expression and the proliferative activity of the HepG2 human hepatocellular carcinoma cell line.

BACKGROUND/AIMS: Gamma aminobutyric acid (GABA) is a potent inhibitory neurotransmitter with growth regulatory properties. Recent data indicate that increased GABAergic activity inhibits hepatocyte proliferation in regenerating livers. In the present study, we aimed to investigate whether GABA inhibits the growth of malignant hepatocytes. METHODS: Increasing concentrations of muscimol (0.05-50 microM), a specific GABA(A) receptor agonist, were added to HepG2 human hepatocellular carcinoma cells and alpha-fetoprotein (AFP) and albumin mRNA expression were determined for varying periods of time (maximum 24 h) thereafter. Cell proliferation was also documented after 48 h of exposure to muscimol. RESULTS: Muscimol significantly (p<0.0001) decreased AFP mRNA expression (maximum decrease: 65% below baseline values) without affecting albumin mRNA expression. However, the effect on AFP mRNA was transient (maximum duration: 3-6 h) and not associated with changes in cell proliferation. Because preliminary data indicate that GABA(A) receptor activity is markedly downregulated in malignant hepatocytes, transfection studies were performed wherein HepG2 cells were cotransfected with GABA(A) receptor beta2 and beta2 subunit genes in a pCDM8 expression vector or vector alone followed by re-exposure to either muscimol (5 betaM) or saline. In this series of experiments, in addition to AFP mRNA inhibition being as extensive and more prolonged (maximum duration: 6-12 h) in muscimol-treated, GABA(A) receptor-transfected cells, proliferative activity was also significantly inhibited when compared to saline-treated GABA(A) receptor-transfected controls (p<0.01) and muscimol-treated cells transfected with vector alone (p<0.005). CONCLUSION: The results of this study indicate that increased GABAergic activity inhibits AFP mRNA expression and cell proliferation in this malignant hepatocyte cell line.